Prebiotic Effect of Eicosapentaenoic Acid Treatment for Colorectal Cancer Liver Metastases

NCT04682665 | Completed DMC FDA Drug

• 2 other identifiers: 20/YH/03061R01CA243454-01A1
• Study Type: observational
• Target: 81
• Locations: 1 country
• Sites: 2

Brief Summary

A significant proportion of patients who undergo liver surgery to remove bowel cancer that has spread to the liver (metastases) develop disease recurrence and die from the disease. The EMT2 study (NCT03428477) is a clinical trial of the omega-3 fatty acid EPA, investigating whether patients who EPA ethyl ester remain free of disease recurrence for longer than those taking placebo. Recent data suggest that the anti-cancer effect of EPA may result from changes to the microbiota (gut bacteria) which lead to an improved anti-cancer response by the immune system. This study will collect biospecimens (stool, urine, blood, tumour tissue) from participants in the EMT2 trial in order to interrogate the microbiome and immune mechanisms associated with EPA treatment, in relation to participant survival. Insights from this study will identify those most likely to benefit from treatment, leading to more targeted, personalised use of EPA.

Conditions

Colon Cancer Liver Metastasis

Keywords

Colon Cancer; Liver Metastases; Microbiome

Outcome Measures

Primary Outcomes (9)

• Abundance of individual bacterial taxa in the gut microbiome (eg. Bifidobacterium, Lactobacillus, and Fusobacterium) in stool samples.

  16S rRNA and metagenomic methods

  A) Change between baseline (pre-treatment) and before liver surgery. B) Change between baseline (pre-treatment) and 6 months after liver surgery. C) Change between baseline (pre-treatment) and time points up to two years follow up.

• Microbial gene expression in stool samples

  Bacterial gene expression analysis

  A) Change between baseline (pre-treatment) and before liver surgery. B) Change between baseline (pre-treatment) and 6 months after liver surgery. C) Change between baseline (pre-treatment) and time points up to two years follow up.

• Levels of polyunsaturated fatty acids and lipid mediators in stool samples

  Liquid chromatography-mass spectrometric measurement of lipids

  A) Change between baseline (pre-treatment) and before liver surgery. B) Change between baseline (pre-treatment) and 6 months after liver surgery. C) Change between baseline (pre-treatment) and time points up to two years follow up.

• Relationship between changes in the gut microbiome induced by EPA and survival of patients

  16S rRNA and metagenomic methods

  A) Change between baseline (pre-treatment) and before liver surgery. B) Change between baseline (pre-treatment) and 6 months after liver surgery. C) Change between baseline (pre-treatment) and time points up to two years follow up.

• Treg cells and myeloid-derived suppressor cells in colorectal cancer liver metastasis tissue

  Immunohistochemistry and flow cytometry for immune cell populations

  A) Change between baseline (pre-treatment) and before liver surgery. B) Change between baseline (pre-treatment) and 6 months after liver surgery. C) Change between baseline (pre-treatment) and time points up to two years follow up.

• Levels of expression of immune checkpoint regulators in colorectal cancer liver metastasis tissue

  Immunohistochemistry for CTLA-4, TIGIT, TIM-3, PD-1 in colorectal cancer liver metastasis tissue

  A) Change between baseline (pre-treatment) and before liver surgery. B) Change between baseline (pre-treatment) and 6 months after liver surgery. C) Change between baseline (pre-treatment) and time points up to two years follow up.

• Blood levels of chemokines and lipid mediators

  Immunoassay and mass spectrometry of chemokines (plasma CCL2) and lipid metabolites (urinary PGE-M)

  A) Change between baseline (pre-treatment) and before liver surgery. B) Change between baseline (pre-treatment) and 6 months after liver surgery. C) Change between baseline (pre-treatment) and time points up to two years follow up.

• Effect of human faecal samples from patients treated with EPA or placebo on tumour burden in gnotobiotic mice with colorectal cancer liver metastasis

  Liver tumour size

  A) Change between baseline (pre-treatment) and before liver surgery. B) Change between baseline (pre-treatment) and 6 months after liver surgery. C) Change between baseline (pre-treatment) and time points up to two years follow up.

• Effect of human faecal samples from patients treated with EPA or placebo on anti-tumour immune response in gnotobiotic mice with colorectal cancer liver metastasis

  Flow cytometry and immunohistochemistry for immune cell populations and cytokine/chemokine levels

  A) Change between baseline (pre-treatment) and before liver surgery. B) Change between baseline (pre-treatment) and 6 months after liver surgery. C) Change between baseline (pre-treatment) and time points up to two years follow up.

Study Arms (2)

Experimental

Patients randomized to the experimental arm of the EMT2 trial, receiving Icosapent Ethyl (EPA-EE) according to the EMT2 protocol.

Drug: Icosapent Ethyl Oral Capsule

Placebo comparator

Patients randomized to the placebo comparator arm of the EMT2 trial, receiving placebo capsules according to the EMT2 protocol.

Other: Placebo

Interventions

Icosapent Ethyl Oral Capsule DRUG

Soft gelatin capsules containing 1g pure EPA-EE. Administered as 4g per day to be taken as 2 capsules in the morning and 2 capsules in the evening.

Experimental

Placebo OTHER

Soft gelatin capsules containing light mineral oil. 4 capsules to be taken per day (2 in the morning and 2 in the evening).

Placebo comparator

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Any participant who has already been enrolled in the EMT2 trial is eligible for inclusion in the biospecimen collection study.

Sponsors & Collaborators

• University of Leeds: lead
• National Cancer Institute (NCI): collaborator
• Massachusetts General Hospital: collaborator
• Massachusetts Institute of Technology: collaborator
• Harvard School of Public Health (HSPH): collaborator
• University of Bradford: collaborator

Study Sites (2)

St James's University Hospital

Leeds, United Kingdom

Location

University of Liverpool

Liverpool, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, stool, urine, tumour tissue (colorectal cancer liver metastases).

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

eicosapentaenoic acid ethyl ester

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Mark Hull

  University of Leeds

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Gastroenterology

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 24, 2020
• Study Start: September 16, 2021
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: December 4, 2024

Record last verified: 2024-12

Locations

GB (2)